Elevated drug saliva levels suggest a "depot-like" effect in subjects treated with sublingual buprenorphine.
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Biomedical subjects
Publications and source records attributed to R E Johnson.
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A diuretic effect of the pentapeptide BW942C [Tyr-D-Met(O)-Gly-pNO2-Phe-Pro-NH2 HCl] was demonstrated in humans and rats; it was characterized pharmacologically using whole animal, isolated tissue and in vitro binding studies. A single 2-mg dose of BW942C increased urine output 5-fold over control values in humans. In Long-Evans rats, BW942C produced a biphasic dose-response curve for urine output with lower doses increasing and higher doses suppressing output. Low doses of naltrexone antagonized the antidiuresis, and high doses antagonized the diuresis produced by BW942C. BW942C was less efficacious in producing diuresis than the full kappa agonists bremazocine and U50,488H (trans-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]- benzeneacetamide methanesulfonate, hydrate). Furthermore, BW942C antagonized the diuretic effects of bremazocine and U50,488H. Rats tolerant to U50,488H-induced diuresis were cross-tolerant to BW942C. In Brattleboro rats, which are unable to synthesize vasopressin, BW942C failed to produce a diuretic effect, demonstrating the necessity of vasopressin for its diuretic response. In the kappa-selective rabbit vas deferens bioassay, BW942C was less efficacious than a full agonist, it was antagonized by naloxone and BW942C in nondepressant doses antagonized a full agonist. In binding studies, BW942C had the highest affinity for mu and delta opioid receptors and an intermediate affinity for kappa opioid receptors. The data suggest that BW942C has the property of a partial kappa opioid agonist in addition to being a mu agonist.
This report compares the morbidity, health care and drug utilization, and health status of random samples of HMO-enrolled Medicare beneficiaries ages 65-79, and 80 and over. The population represented 3,683 person-years of Kaiser Permanente eligibility (59.2 percent female). Those 80 and over were 20 percent of the person-years (64.1 percent female). The effects of age and sex on morbidity and utilization were analyzed using log linear models that controlled for eligibility, and using two-way analyses of variance of rates. Few differences were found in the morbidity experiences and utilization rates of the two age groups. Indicators of self-reported health status did differ. The findings support the idea that noninstitutionalized very old persons are the healthy survivors of their cohort. Their health care needs may not be much different than younger old persons in terms of the types and amounts of health care services needed.
The prevalence of infection with the genital herpes simplex virus type 2 (HSV-2) has been difficult to ascertain, primarily because of the large percentage of subclinical cases and the limitations in specificity of serologic assays for antibody to HSV-2. To obtain an improved estimate of the distribution of HSV-2 infection in the United States, we used an HSV type-specific antibody assay to test serum samples from 4201 participants in the second National Health and Nutrition Examination Survey. The results in our sample indicate that in the period from 1976 to 1980, 16.4 percent of the U.S. population 15 to 74 years of age (approximately 25 million persons) was infected with HSV-2 (95 percent confidence interval, 14.2 to 18.6 percent). Age and race were the demographic factors associated most strongly with the presence of HSV-2 antibody. The prevalence of the antibody increased from less than 1 percent in the group under 15 years old to 20.2 percent in the group 30 to 44 years old; it increased only slightly thereafter. In the oldest group, 60 to 74 years of age, the prevalence was 19.7 percent in whites and 64.7 percent in blacks. Among blacks of all age groups, but not whites, higher rates were observed in women than in men. The associations were weaker with respect to marital status, income, education, urban residence, and region of the country. After control for age, sex, and race, only the association with marital status remained significant; the rate was increased in persons previously married--i.e., divorced, separated, or widowed. We conclude that the prevalence of HSV-2 infection in the United States is higher than has previously been recognized and that many infections with this sexually transmitted virus may be subclinical.
A new, rapid dose-induction procedure was used in the evaluation of buprenorphine hydrochloride (buprenorphine) as a treatment for opiate dependence. Nineteen heroin-dependent men were given buprenorphine sublingually in ascending daily doses of 2, 4, and 8 mg and then maintained on 8 mg daily. The observations of the transition from heroin to buprenorphine for the first 4 days are described. During this period, subjects reported significantly elevated ratings of "good effects" and feelings of "overall well-being" and decreased ratings of "overall sickness." Data from subscales of the Addiction Research Center Inventory indicated increasing euphoria and decreasing dysphoria and sedation after buprenorphine administration. Subjects and observers consistently identified buprenorphine as an opiate and not as an opiate antagonist. These findings indicate that a rapid dose induction with buprenorphine is acceptable to heroin-dependent persons and that it causes minimal withdrawal symptoms.
To compare the pharmacologic profiles of sublingually and subcutaneously administered buprenorphine, 10 healthy male subjects with histories of opiate abuse were given sublingually administered buprenorphine (1, 2, and 4 mg), subcutaneously administered buprenorphine (1 and 2 mg), and placebo in a double-blind, double-dummy, placebo-controlled study. All active buprenorphine dosages produced a significant degree of miosis but no significant changes in body temperature, blood pressure, or respiratory or heart rate. Buprenorphine produced varying degrees of euphoria related to dose and route of administration but little dysphoria and sedation, as assessed by subscales of the Addiction Research Center Inventory. Subject "liking" for buprenorphine was reported by both observers and subjects. The relative potency of sublingually to subcutaneously administered buprenorphine was calculated for both physiologic and behavioral parameters and found to be approximately two thirds. The results indicated that both sublingual and subcutaneous buprenorphine have a similar profile of effects in opiate abusers.
We used the 1978 National Health and Nutrition Examination Survey to examine the prevalence of positive syphilis serologies in the US population. Analysis of risk markers--gender, age, marital status, education, income, and residence--indicates that all except gender are associated with syphilis seroreactivity, independent of race. Controlling for associated risk markers, the Black-White odds ratio of syphilis seroreactivity is 4.7 (95% CI = 2.7, 8.2). Current knowledge of racial differences in sexual and health care behavior does not explain the Black-White difference in the prevalence of syphilis seroreactivity.
The authors conducted a study to identify the nuances and frequencies of use for various neutral casting techniques. This was accomplished through a survey questionnaire that was sent to 300 podiatric physicians and 48 orthotic laboratories selected at random. To the best of the authors' knowledge, this has not been done previously. Survey results indicated that a difference of opinion exists among respondents in identifying critical factors in neutral position casting.
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Benzalkonium chloride (BAK), sodium lauryl sulfate (SLS), chlorhexidine digluconate, thimerosal and polyaminopropyl biguanide were tested for their effects on the rate of corneal epithelial regrowth after mechanical lesions, and BAK and SLS after heptanol-generated lesions in rabbit corneas. Only 1.3% SLS reduced the rate of epithelial healing after three times a day drop application as determined using planar measures of epithelial regrowth. SLS, a common ingredient in soups and shampoos, should be used carefully where a lesion or wound is present in the corneal epithelium.
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It was previously shown that when rabbit skeletal myofibrils are titrated with Mg2+ AMPPNP under conditions that result in the dissociation of cross-bridges from the thin filaments (i.e. 50% ethylene glycol, 0 degrees C), Ca2+-sensitive, biphasic binding is observed. These titrations have been repeated using myofibrils from which the troponin C has been selectively removed. The disappearance of both Ca2+ sensitivity and biphasic binding is taken as evidence that the Ca2+ sensitivity is due to Ca2+ binding to troponin C and the biphasic binding of Mg2+ AMPPNP observed in intact myofibrils is not due to packing constraints or steric hindrance.
Large doses of naloxone (150-300 mg), placebo, and morphine (15-30 mg) were given intramuscularly to human volunteers and compared using measures of subjective feeling states, physiological measures and discriminative features. Plasma prolactin responses after naloxone 210 mg and placebo were compared. The subjective measures and discriminative features of naloxone revealed that the drug is subtly psychoactive but the stimulus is vague and cannot be identified clearly as an opioid agonist or antagonist in nondependent opioid-using volunteers. The physiologic and prolactin responses closely resembled opiate agonist activity. We conclude that naloxone in this dose range may act as an opiate agonist in man.
The efficacy of buprenorphine and methadone was compared in the outpatient detoxification of heroin addicts. Forty-five patients were randomized to receive either sublingual buprenorphine or oral methadone under double-dummy and double-blind conditions to study the pharmacology of buprenorphine in a 90-day detoxification protocol. The patients were administered either 2 mg buprenorphine or 30 mg methadone for 3 weeks followed by 4 weeks of dose reductions and 6 weeks of placebo medication. No significant between-group differences were seen on measures of treatment retention, drug use, or symptom report. During the hydromorphone challenge, methadone attenuated opioid effects to a greater extent than did buprenorphine on both physiologic (pupil constriction) and self-report measures. However, this did not result in greater abuse of illicit opioid drugs by subjects taking buprenorphine. The results of this clinical trial indicated that buprenorphine was acceptable to patients and as effective as methadone in the detoxification treatment of heroin addicts.